An estimated 600,000 African-Americans have chronic hepatitis C virus (HCV) infection, representing 22% of the total infected population in the U.S. Prior studies suggest African-Americans with chronic HCV infection have a lower rate of response to anti-viral therapy than non-Hispanic whites. The difference is, in part, related to the predominance of genotype 1 among African-Americans. Response rates appear to higher with combination interferon plus ribavirin than with interferon monotherapy. However, the studies to date have included very low numbers of African-American subjects (<5%), limiting the interpretation of response rates. In the proposed study, the rate of sustained virological response (viral clearance) to pegylated interferon plus ribavirin will be compared in 200 African Americans and 200 non-Hispanic whites. The clinical, biochemical, or virological factors which predict sustained virological response to anti-viral therapy and reduced inflammatory activity on liver histology will be determined and early viral kinetics will be examined as a predictor of response or non-response. This collaborative study involving eight clinical centers will also provide the clinical data and biological specimens to coinvestigators focused on determining the virological, cellular, immunological and genetic factors that underlie the response to antiviral therapy in hepatitis C. Pegylated interferon plus interferon is chosen as the anti-viral intervention because combination therapy has been shown to be superior to interferon monotherapy and preliminary data indicate pegylated interferons are superior to standard interferons. Additionally, the convenience of once weekly dosing may improve compliance. Participants will undergo liver biopsy prior to study entry and at end of follow-up (96 wks). Virological analyses include HCV RNA quantitation (qualitative and quantitative) and HCV genotyping. Baseline assessments include demographic (using self-reporting of race/ethnicity) risk factor assessment, biochemistry and hematology, quality-of-life and fatigue assessments. Follow-up visits will include adverse events inquiry, assessment of compliance, collection of serum and peripheral blood mononuclear cells for virological analyses, and repeat liver biopys 48 weeks after completion of treatment. All study visits, including liver biopsies, will occur in the General Clinical Research Center. The primary treatment outcome is loss of HCV RNA at 96 weeks (48 weeks post-treatment). Secondary endpoints include loss of HCV RNA at 48 weeks; normalization of liver enzymes and improvement in histological inflammatory indices at 96 weeks; and tolerability (assessed by? adverse event inquiry and fatigue questionnaires). This study will accurately define the sustained response rates with optimal anti-viral therapy in African-Americans and provide important insights into the factors underlying differences in response compared to non-Hispanic whites. Moreover, the methodologies developed for patient outreach within the context of this collaborative study will serve as a model for enhancing participation of African Americans in clinical research.